1. Field of the Invention
The invention relates to a latanoprost ophthalmic solution and a method of preparing same, which is chemically stable at room temperature, and which offers greater efficiency, safety and performance in the treatment of distinct ailments of the eye.
2. Description of Prior Art
The analogs of the prostaglandins are some of the most recent additions to the list of hypotensive ocular medicines available for the treatment of glaucoma. The main mechanism of action of these agents for the reduction of intraocular pressure is, as has been observed in the performed studies, by means of the increase of the elimination of the aqueous humor by means of the conventional path or uveosderal path. This mechanism consists of the action of these compounds on specific prostanoid receptors of the ciliary muscles and, furthermore, it favors the biosynthesis of metalloproteins of the uterus, a family of proteins that can attach themselves to the components of the extracellular uterus. The above alters the content of collagen in the ciliary muscle, whereby there is a reduction in the hydraulic resistance of the uveoscleral path.
Latanoprost is an analog of the prostaglandin F2α which is used to treat the open angle glaucoma; it is a selective agonist of the FP prostanoid receptor which reduces the intraocular pressure, increasing the outflow of the aqueous humor. Studies on animals and humans indicate that the main mechanism of action is an increased uveoscleral outflow.
Latanoprost is a colorless or slightly yellow oily liquid, highly soluble in acetonitrile and freely soluble in acetone, ethanol, ethyl acetate, isopropanol, methanol and octanol. It is practically insoluble in water. Latonoprost is the isopropilic ester of the prostaglandin F2α 17-phenyl-13,14dihydro (17-phenyl-13,14dihydro PGF2α). It is presented in the form of prodrug of free acid, which is a potent agonist of the FP receptors of the eye. Latanoprost reduces intraocular pressure in patients with glaucoma.
Latanoprost is a prodrug that is well absorbed via the cornea, being activated by hydrolysis to the active form of latanoprost acid. The peak concentration in the aqueous humor is reached 2 hours after local administration. The latanoprost acid is practically not metabolized in the eye. Its principal metabolism occurs in the liver giving inactive metabolites that are mostly excreted in the urine. The plasmatic mid life in humans is of 17 minutes.
The formula of latanoprost is C26H40O5 and it has a molecular weight of 432.85, it is an isopropilic ester prodrug, which alone is inactive, but following hydrolysis it becomes biologically active. The prodrug is fully absorbed via the cornea and all the drug that enters the aqueous humor is hydrolyzed during the passage through the cornea.
Studies on humans indicate that the maximum concentration in the aqueous humor is reached approximately two hours following its administration.
It has been demonstrated that one sole daily application of latanoprost (0.005%) is most effective, or at least as effective as a double daily application of other agents utilized in glaucoma therapy, in the reduction of the intraocular pressure in patients with open angle glaucoma or ocular hypertension. Most patients treated with latanoprost reached a neutral level of intraocular pressure after 6 months of treatment in relation to patients treated with other hypotensive agents, observing a reduction in the intraocular pressure of at least 30% in 52% of the patients treated with latanoprost.
Another benefit of latanoprost seems to be a more uniform circadian reduction of intraocular pressure, while timolol is less effective during the night. Dorzolamide is less effective than latanoprost but permits a significant reduction in nocturnal intraocular pressure.
There are studies in which latanoprost has shown additive effects ranging from 13% to 37% when combined with timolol which exceed the effects shown by joint therapies using combinations of timolol with pilocarpine, brimonidine and dorzolamide. There also exists a precedent of unoprostone combined with β-blockers where significant hypotensive effects were found.
Studies have been performed by distinct investigators in order to compare the effectiveness of latanoprost with respect to unoprostone as hypotensive agents, observing better results in patients treated with latanoprost, presenting similar side effects.
Medicines applied to the surface of the eye should meet certain characteristics of pH, osmolarity, conductivity, continuance time and clarity of vision following application, in order to be accepted by patients. However, in the case of latanoprost, and other therapeutic active ingredients insoluble in water, are generally prepared in solutions that present numerous inconveniences, with the most important one being the accelerated degeneration of the active ingredient at room temperature.